The Gα12-RGS RhoGEF-RhoA signalling pathway regulates neurotransmitter release in C. elegans

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Abstract
In Caenorhabditis elegans adults, the single Rho GTPase orthologue, RHO‐1, stimulates neurotransmitter release at synapses. We show that one of the pathways acting upstream of RHO‐1 in acetylcholine (ACh)‐releasing motor neurons depends on Gα12 (GPA‐12), which acts via the single C. elegans RGS RhoGEF (RHGF‐1). Activated GPA‐12 has the same effect as activated RHO‐1, inducing the accumulation of diacylglycerol and the neuromodulator UNC‐13 at release sites, and increased ACh release. We showed previously that RHO‐1 stimulates ACh release by two separate pathways—one that requires UNC‐13 and a second that does not. We show here that a non‐DAG‐binding‐UNC‐13 mutant that partially blocks increased ACh release by activated RHO‐1 completely blocks increased ACh release by activated GPA‐12. Thus, the upstream GPA‐12/RHGF‐1 pathway stimulates only a subset of RHO‐1 downstream effectors, suggesting that either the RHO‐1 effectors require different levels of activated RHO‐1 for activation or there are two distinct pools of RHO‐1 within C. elegans neurons.